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Detection of MicroRNAs in Microglia by Real-time PCR in Normal CNS and During Neuroinflammation
Published on: July 23, 2012
miR-124 Contributes to the functional maturity of microglia
Adam J Svahn1, Jean Giacomotto1, Manuel B Graeber1,2
1Brain and Mind Research Institute, Sydney Medical School, University of Sydney, Sydney, Australia.
Abstract:
During early development of the central nervous system (CNS), a subset of yolk-sac derived myeloid cells populate the brain and provide the seed for the microglial cell population, which will self-renew throughout life. As development progresses, individual microglial cells transition from a phagocytic amoeboid state through a transitional morphing phase into the sessile, ramified, and normally nonphagocytic microglia observed in the adult CNS under healthy conditions. The molecular drivers of this tissue-specific maturation profile are not known. However, a survey of tissue resident macrophages identified miR-124 to be expressed in microglia. In this study, we used transgenic zebrafish to overexpress miR-124 in the mpeg1 expressing yolk-sac-derived myeloid cells that seed the microglia. In addition, a systemic sponge designed to neutralize the effects of miR-124 was used to assess microglial development in a miR-124 loss-of-function environment. Following the induction of miR-124 overexpression, microglial motility and phagocytosis of apoptotic cells were significantly reduced. miR-124 overexpression in microglia resulted in the accumulation of residual apoptotic cell bodies in the optic tectum, which could not be achieved by miR-124 overexpression in differentiated neurons. Conversely, expression of the miR-124 sponge caused an increase in the motility of microglia and transiently rescued motility and phagocytosis functions when activated simultaneously with miR-124 overexpression. This study provides in vivo evidence that miR-124 activity has a key role in the development of functionally mature microglia.
Insights
MicroRNA-124 (miR-124) is crucial for microglial maturation in the central nervous system (CNS). This study shows miR-124 regulates microglial motility and phagocytosis, essential for CNS development and health.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- Microglia, the resident immune cells of the central nervous system (CNS), originate from yolk-sac derived myeloid cells during early development.
- Microglial cells undergo a maturation process from a phagocytic amoeboid state to a ramified, nonphagocytic state in the adult CNS.
- The molecular mechanisms driving microglial maturation remain largely unknown, although miR-124 has been identified in microglia.
Purpose of the Study:
- To investigate the role of microRNA-124 (miR-124) in the development and functional maturation of microglia in vivo.
- To determine if miR-124 regulates microglial motility and phagocytic activity during CNS development.
Main Methods:
- Utilized transgenic zebrafish to overexpress miR-124 in yolk-sac derived myeloid cells, the precursors of microglia.
- Employed a systemic miR-124 sponge in zebrafish to create a loss-of-function environment for miR-124.
- Assessed microglial motility, phagocytosis of apoptotic cells, and accumulation of cellular debris in the optic tectum.
Main Results:
- Overexpression of miR-124 in microglia significantly reduced their motility and phagocytosis of apoptotic cells.
- miR-124 overexpression led to the accumulation of apoptotic cell bodies in the optic tectum, indicating impaired clearance.
- Inhibition of miR-124 (using a sponge) increased microglial motility and partially rescued functions affected by miR-124 overexpression.
Conclusions:
- miR-124 plays a critical role in regulating the functional maturation of microglia within the developing CNS.
- miR-124 activity is essential for maintaining normal microglial motility and phagocytic clearance of apoptotic debris.
- This study provides in vivo evidence for miR-124 as a key molecular driver of microglial development and function.
